On February 3, 2020 GlaxoSmithKline plc reported that the European Medicines Agency (EMA) validated the marketing authorisation application (MAA) for belantamab mafodotin for the treatment of patients with relapsed or refractory multiple myeloma whose prior therapy included an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody (Press release, GlaxoSmithKline, FEB 3, 2020, View Source [SID1234553759]). Belantamab mafodotin was accepted for accelerated assessment by the EMA’s Committee for Human Medicinal Products (CHMP).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Accelerated assessment is granted if the CHMP determines the treatment is of major interest from a public health perspective and represents a therapeutic innovation. Validation of the MAA confirms that the submission is accepted and begins the formal review process by the CHMP.

The MAA is based on data from the pivotal DREAMM-2 (DRiving Excellence in Approaches to Multiple Myeloma) study. Full results from the study, recently published in The Lancet Oncology, demonstrated a 31% overall response rate (ORR) with a 2.5 mg/kg regimen of single-agent belantamab mafodotin in heavily pre-treated patients with multiple myeloma who were refractory to an immunomodulatory drug and a proteasome inhibitor and were refractory and/or intolerant to an anti-CD38 antibody. The safety and tolerability profile was consistent with previously reported data on belantamab mafodotin. [1]

More than 48,000 people in the European Union were diagnosed with multiple myeloma in 2018.[2] Belantamab mafodotin was granted PRIME designation in 2017 by the EMA, a programme that is intended to facilitate development of investigational medicines that have shown clinical promise for conditions where there is significant unmet need.

About multiple myeloma
Multiple myeloma is the second most common blood cancer and is generally considered treatable, but not curable.[3] Research into new therapies is needed as multiple myeloma commonly becomes refractory to available treatments.[4]

About B-cell maturation antigen (BCMA)
The normal function of BCMA is to promote plasma cell survival by transduction of signals from two known ligands, BAFF (B-cell activating factor) and APRIL (a proliferation-inducing ligand). This pathway has been shown to be important for myeloma cell growth and survival. BCMA expression is limited to B cells at later stages of development. BCMA is expressed at varying levels in myeloma patients and BCMA membrane expression is universally detected in myeloma cell lines.[5]

About the DREAMM clinical trial programme for belantamab mafodotin (GSK2857916)
Belantamab mafodotin is an investigational immunoconjugate comprising a humanised anti-B cell maturation antigen (BCMA) monoclonal antibody conjugated to the cytotoxic agent auristatin F via non-cleavable linker. The drug linker technology is licensed from Seattle Genetics; monoclonal antibody is produced using POTELLIGENT Technology licensed from BioWa.

Belantamab mafodotin is not currently approved for use anywhere in the world.

Trial Name

GSK ID/NCT ID

Status

Design

DREAMM-1

117159/ NCT02064387

Completed

A Phase I Open-label Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, Immunogenicity and Clinical Activity of Belantamab Mafodotin (GSK2857916) in Subjects with Relapsed/Refractory Multiple Myeloma and Other Advanced Hematologic Malignancies Expressing BCMA

DREAMM-2

205678/ NCT03525678

Active, not recruiting

A Phase II Study to Investigate the Efficacy and Safety of Two Doses of Belantamab Mafodotin (GSK2857916) in Subjects with Relapsed/Refractory Multiple Myeloma Who are Refractory to a Proteasome Inhibitor and an Immunomodulatory Agent and Have Failed Prior Treatment with an Anti-CD38 Antibody

DREAMM-3

207495

Planned

A Phase III Open-Label, Randomized Study to Evaluate the Efficacy and Safety of Belantamab Mafodotin (GSK2857916) Compared to Pomalidomide plus low-dose Dexamethasone (Pom/Dex) in Participants with Relapsed/Refractory Multiple Myeloma

DREAMM-4

205207/ NCT03848845

Recruiting

A Phase I/II Single Arm Open-Label Study to Explore Safety and Clinical Activity of Belantamab Mafodotin (GSK2857916) Administered in Combination with Pembrolizumab in Subjects with Relapsed/Refractory Multiple Myeloma

DREAMM-5

208887/

NCT04126200

Recruiting

A Phase I/II, Randomized, Open-label Platform Study of Belantamab Mafodotin (GSK2857916) with Innovative Combination Anti-Cancer Treatments in Participants with Relapsed/Refractory Multiple Myeloma

DREAMM-6

207497/ NCT03544281

Recruiting

A Phase I/II Randomized Study to Evaluate Safety, Tolerability and Clinical Activity of Belantamab Mafodotin (GSK2857916) Administered in Combination with Lenalidomide plus Dexamethasone (Arm A), or in Combination with Bortezomib plus Dexamethasone (Arm B) in Subjects with Relapsed/Refractory Multiple Myeloma

DREAMM-7

207503

Planned

A Phase III Study of Belantamab Mafodotin (GSK2857916) Administered in Combination with Bortezomib plus Dexamethasone versus Daratumumab, Bortezomib, and Dexamethasone in Participants with Relapsed/Refractory Multiple Myeloma

DREAMM-8

207499

Planned

A Phase III, Multicentre, Open-Label, Randomized Study to Evaluate the Efficacy and Safety of Belantamab Mafodotin (GSK2857916) in Combination with Pomalidomide plus Low-Dose Dexamethasone (BPd) versus Pomalidomide plus Bortezomib and Low-Dose Dexamethasone (PVd) in Participants with Relapsed/Refractory Multiple Myeloma

DREAMM-9

209664/ NCT04091126

Recruiting

A Phase III Study of Belantamab Mafodotin (GSK2857916) Administered in Combination with Bortezomib plus Lenalidomide and Low-Dose Dexamethasone (VRd) vs. VRd in Participants with Newly Diagnosed Multiple Myeloma who are Ineligible for Transplant

DREAMM-10

207500

Planned

A Phase III Study of Belantamab Mafodotin (GSK2857916) Administered in Combination with a Novel Agent versus SoC

ISS / GSK Co-Sponsored Study

209418/ NCT03715478

Recruiting

A Phase I/II Dose-escalation and Dose-expansion Study of Belantamab Mafodotin (GSK2857916) Administered in Combination with Pomalidomide plus Low-dose Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma Who Have Received Two or More Prior Lines of Therapy That Must Have Included Lenalidomide and a Proteasome Inhibitor

GSK in Oncology
GSK is focused on maximising patient survival through transformational medicines. GSK’s pipeline is focused on immuno-oncology, cell therapy, cancer epigenetics, and synthetic lethality. Our goal is to achieve a sustainable flow of new treatments based on a diversified portfolio of investigational medicines utilising modalities such as small molecules, antibodies, antibody drug conjugates and cells, either alone or in combination.

On February 3, 2020 Crescendo Biologics Ltd (Crescendo), the drug developer of novel, targeted, T cell enhancing therapeutics, reported the appointment of Dr Kenji Hashimoto as the Company’s Chief Medical Officer (CMO) (Press release, Crescendo Biologics, FEB 3, 2020, View Source [SID1234553757]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Dr Hashimoto will oversee Crescendo’s clinical development strategy and medical affairs. His appointment marks the next stage of Crescendo’s development, as it focuses on building out its clinical capabilities and bringing its lead programme, CB307, to the clinic later this year. He replaces Dr Pavel Pisa as CMO, who has transitioned into the role of scientific adviser.

Dr Hashimoto joins the Company with over 15 years’ experience in oncology and immuno-oncology. Prior to joining Crescendo, he led the clinical development of a checkpoint inhibitor in renal cell carcinoma at Roche, with responsibility for multiple late phase clinical trials. Prior to that, he was Clinical Research Physician at Chugai Pharma Europe, leading clinical development for a bispecific T cell engaging antibody programme as well as other early phase projects. He was previously Chief Resident in Medical Oncology at the National Cancer Centre Hospital, Tokyo. He has a PhD in medical oncology from the University of Oxford and a medical degree from Gunma University in Japan.

The Company’s lead programme, CB307, is a CD137 (4-1BB) x PSMA bispecific for PSMA-positive tumours.

Theodora Harold, CEO of Crescendo Biologics, said:

"Kenji has considerable immuno-oncology expertise and an impressive track record in leading clinical development programmes. This experience will be crucial as we progress our pipeline of innovative, first in class, T cell enhancing programmes. On behalf of the Board, I would like to welcome Kenji to the Crescendo team at this exciting time for the Company as we take our first programme into the clinic later this year.

"I would also like to thank Pavel for his valuable contribution to the Company as CMO and look forward to working with him as one of our scientific advisers."

Kenji Hashimoto, CMO of Crescendo Biologics commented:

"I am delighted to be joining Crescendo at this exciting time. Crescendo has established an important position in the CD137 (4-1BB) space. I look forward to helping the Company advance its pipeline of novel T cell enhancing programmes, and to helping translate its next generation programmes into therapeutics for real patient benefit."

On February 3, 2020 Clovis Oncology, Inc. (NASDAQ: CLVS) reported that Rubraca (rucaparib) is now available and reimbursed in France (Press release, Clovis Oncology, FEB 3, 2020, View Source [SID1234553756]). Rubraca (rucaparib) is an option for monotherapy maintenance treatment for adults with relapsed, platinum-sensitive high-grade epithelial ovarian, fallopian tube or primary peritoneal cancer that has responded to platinum-based chemotherapy.2 Rucaparib is indicated for eligible patients regardless of BRCA status, which means it can be prescribed for women who harbor a BRCA mutation or who are BRCA wild-type.2

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"This is excellent news as this represents an important new option for patients with relapsed ovarian cancer who have responded to platinum-based chemotherapy," said a spokesperson for IMAGYN, the only French network of patient associations involved in the fight against ovarian cancer and gynecological tumors. "For too long, ovarian cancer treatment options beyond chemotherapy, surgery and anti-angiogenic therapy have been limited, and today’s announcement means that eligible women with ovarian cancer have more choice in their treatment than ever before."

Approximately 5,000 women are diagnosed with ovarian cancer in France every year, which equates to roughly 14 every day.3 Ovarian cancer is the eighth most common cancer in women and the fourth most fatal cancer in France.4 In addition, approximately 25 percent of ovarian cancer patients harbor a BRCA1/2 mutation in the tumor, correlating to improved outcomes to platinum and PARP inhibitors therapy.5,6 The majority of women diagnosed with ovarian cancer are BRCA wild-type; these patients typically have a worse prognosis.5,6 Of those treated with surgery and first line chemotherapy, approximately 70 percent of patients will relapse within the first three years.7

"The availability of rucaparib is good news, as ovarian cancer is a disease often diagnosed at an advanced stage and many women may have a poor prognosis," said Professor Isabelle Ray-Coquard, President of the GINECO Group, which specializes in clinical and translational research in the field of women’s cancers, and sets up and coordinates clinical trials in France and abroad. "Patients with relapsed ovarian cancer may have many debilitating symptoms, and it is important that new treatments such as rucaparib are made available to the eligible patients that may benefit from them."

The European Union (EU) authorization is based on data from the pivotal phase 3 ARIEL3 clinical trial, which found that rucaparib significantly improved PFS in all ovarian cancer patient populations studied.1 ARIEL3 successfully achieved its primary endpoint of extending investigator-assessed PFS versus placebo in all patients treated (intention-to-treat, or ITT), population, regardless of BRCA status (median 10.8 months vs 5.4 months).1,2 In this population, the risk of progression or death has been decreased by 64%.1 In addition, it successfully achieved the key secondary endpoint of extending PFS by independent radiological review versus placebo in all patients treated (ITT), regardless of BRCA status (median 13.7 months vs 5.4 months).2 The overall safety profile of rucaparib is based on data from 937 patients with ovarian cancer treated with rucaparib monotherapy in clinical trials.2

"The fact that rucaparib is now reimbursed and available in France means there is a new treatment for patients with platinum-sensitive relapsed ovarian cancer," said Dr. Anne Floquet, President of the SFOG, the French Society for Gyneco-Oncology. "I am very proud to have been able to participate in the ARIEL3 study, which demonstrates the effectiveness of rucaparib in improving patients’ progression-free survival. I am also delighted to be able to prescribe this treatment as it may offer benefits for eligible patients."

"We are working to make Rubraca available in multiple countries across Europe, and with the reimbursement and availability of Rubraca in France, it is now a treatment option for eligible patients in Germany, England, Italy, and in France," said Patrick J. Mahaffy, President and CEO of Clovis Oncology. "Rubraca is effective across a broad population of women with relapsed ovarian cancer and is an important step in the ovarian cancer treatment pathway for eligible patients."

About Rubraca (rucaparib)

Rubraca is an oral, small molecule inhibitor of PARP1, PARP2 and PARP3 that is being developed in multiple tumor types, including ovarian and metastatic castration-resistant prostate cancer (mCRPC), as monotherapy, and in combination with other anti-cancer agents. Exploratory studies in other tumor types are also underway.

Rubraca (rucaparib) European Union (EU) authorized use and Important Safety Information

Rubraca is indicated as monotherapy for the maintenance treatment of adult patients with platinum-sensitive relapsed high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) to platinum-based chemotherapy.

Rubraca is indicated as monotherapy treatment of adult patients with platinum sensitive, relapsed or progressive, BRCA mutated (germline and/or somatic), high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have been treated with ≥2 prior lines of platinum-based chemotherapy, and who are unable to tolerate further platinum-based chemotherapy.

Efficacy of Rubraca as treatment for relapsed or progressive EOC, FTC, or PPC has not been investigated in patients who have received prior treatment with a PARP inhibitor. Therefore, use in this patient population is not recommended.

Summary warnings and precautions:

Hematological toxicity

During treatment with Rubraca, events of myelosuppression (anemia, neutropenia, thrombocytopenia) may be observed and are typically first observed after 8–10 weeks of treatment with Rubraca. These reactions are manageable with routine medical treatment and/or dose adjustment for more severe cases. Complete blood count testing prior to starting treatment with Rubraca, and monthly thereafter, is advised. Patients should not start Rubraca treatment until they have recovered from hematological toxicities caused by previous chemotherapy (CTCAE grade ≥1).

Supportive care and institutional guidelines should be implemented for the management of low blood counts for the treatment of anemia and neutropenia. Rubraca should be interrupted or dose reduced according to Table 1 (see Posology and Method of Administration [4.2] of the Summary of Product Characteristics [SPC]) and blood counts monitored weekly until recovery. If the levels have not recovered to CTCAE grade 1 or better after 4 weeks, the patient should be referred to a hematologist for further investigations.

MDS/AML

MDS/AML, including cases with fatal outcome, have been reported in patients who received Rubraca. The duration of therapy with Rubraca in patients who developed MDS/AML varied from less than 1 month to approximately 28 months.

If MDS/AML is suspected, the patient should be referred to a hematologist for further investigations, including bone marrow analysis and blood sampling for cytogenetics. If, following investigation for prolonged hematological toxicity, MDS/AML is confirmed, Rubraca should be discontinued.

Photosensitivity

Photosensitivity has been observed in patients treated with Rubraca. Patients should avoid spending time in direct sunlight because they may burn more easily during Rubraca treatment; when outdoors, patients should wear a hat and protective clothing, and use sunscreen and lip balm with sun protection factor of 50 or greater.

Gastrointestinal toxicities

Gastrointestinal toxicities (nausea and vomiting) are frequently reported with Rubraca, and are generally low grade (CTCAE grade 1 or 2), and may be managed with dose reduction (refer to Posology and Method of Administration [4.2], Table 1 of the SPC) or interruption. Antiemetics, such as 5-HT3 antagonists, dexamethasone, aprepitant and fosaprepitant, can be used as treatment for nausea/vomiting and may also be considered for prophylactic (i.e. preventative) use prior to starting Rubraca. It is important to proactively manage these events to avoid prolonged or more severe events of nausea/vomiting which have the potential to lead to complications such as dehydration or hospitalization.

Embryofetal toxicity

Rubraca can cause fetal harm when administered to a pregnant woman based on its mechanism of action and findings from animal studies. In an animal reproduction study, administration of Rubraca to pregnant rats during the period of organogenesis resulted in embryo-fetal toxicity at exposures below those in patients receiving the recommended human dose of 600 mg twice daily (see Preclinical Safety Data [5.3] of the SPC).

Pregnancy/contraception

Pregnant women should be informed of the potential risk to a fetus. Women of reproductive potential should be advised to use effective contraception during treatment and for 6 months following the last dose of Rubraca (see section 4.6 of the SPC). A pregnancy test before initiating treatment is recommended in women of reproductive potential.

On February 3, 2020 Nippon Kayaku Co., Ltd. (Headquarters: Tokyo, President: Atsuhiro Wakumoto, hereafter, "Nippon Kayaku") and Bayer Yakuhin, Ltd. (Headquarters: Osaka, President: Heike Prinz, hereafter, "Bayer Yakuhin") reported that it signed an agreement on the co-promotion in Japan with regard to Nubeqa (generic name: darolutamide), for which Bayer received regulatory approval from the Ministry of Health, Labor and Welfare (MHLW) for the treatment of patients with non-metastatic castrationresistant prostate cancer (nmCRPC) (Press release, Nippon Kayaku, FEB 3, 2020, View Source [SID1234553749]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Based on this agreement, the medical representatives (MRs) of the two companies will collaborate to provide medical information on Nubeqa. The product will be marketed by Bayer and co-promoted with Nippon Kayaku.

Bayer will expand its prostate cancer portfolio with Nubeqa in addition to Xofigo Injection (generic name: radium-223 dichloride), which was launched in June 2016 as a treatment for CRPC with bone metastases. With the co-promotion agreement with Nippon Kayaku, a leading company in the area of prostate cancer, Bayer will provide appropriate information on Nubeqa to a broad range of healthcare professionals.

Nippon Kayaku has provided products for the treatment of urologic tumors and its respective information since the launch of BleoTM in 1969. Through this joint effort with Bayer Yakuhin to provide healthcare professionals with information on the proper use of Nubeqa, Nippon Kayaku would like to expand treatment options for patients and further contribute to the improvement of healthcare.

Bayer and Nippon Kayaku will promote proper use of Nubeqa and provide information on this product, aiming at further contributing to the treatment of patients with prostate cancer. Nippon Kayaku and Bayer sign agreement for the co-promotion of Nubeqa-2/4-

About Nubeqa
Nubeqa is an androgen receptor inhibitor (ARi) with a distinct chemical structure that binds to the receptor with high affinity and exhibits strong antagonistic activity, thereby inhibiting the receptor function and the growth of prostate cancer cells. The compound is also being investigated in a Phase III study in metastatic hormone-sensitive prostate cancer (ARASENS). Information about these trials can be found at View Source

Nubeqa, which is jointly developed by Bayer and Orion Corporation, a globally operating Finnish pharmaceutical company, has been approved in the U.S., Brazil and Japan under the brand name Nubeqa. Filings in the European Union and other regions are underway or planned.

About castration-resistant prostate cancer (CRPC)
Prostate cancer is the second most commonly diagnosed malignancy in men worldwide.1 In 2018, an estimated 1.2 million men were diagnosed with prostate cancer, and about 358,000 died from the disease worldwide.1 Prostate cancer is the fifth leading cause of death from cancer in men.1 Prostate cancer results from the abnormal proliferation of cells within the prostate gland, which is part of a man’s reproductive system.2 It mainly affects men over the age of 50, and the risk increases with age.3

Treatment options range from surgery to radiation treatment to therapy using hormonereceptor antagonists, i.e., substances that stop the formation of testosterone or prevent its effect at the target location.4 However, in nearly all cases, the cancer eventually becomes resistant to conventional hormone therapy.5

CRPC is an advanced form of the disease where the cancer keeps progressing despite androgen deprivation therapy (ADT) treatment, even when the amount of testosterone is reduced to very low levels in the body.6,7 In men with progressive nmCRPC, a rapid prostate specific antigen (PSA) doubling time has been consistently associated with reduced time to first metastasis and death.6-3/4-

About Oncology at Bayer
Bayer is committed to delivering science for a better life by advancing a portfolio of innovative treatments. The oncology franchise at Bayer now expands to six marketed products and several other assets in various stages of clinical development. Together, these products reflect the company’s approach to research, which prioritizes targets and pathways with the potential to impact the way that cancer is treated.

On February 2, 2020 Children’s Hospital Los Angeles (CHLA) reported that the Margie and Robert E. Petersen Foundation has contributed $25 million to establish an endowment supporting three of the hospital’s signature programs: the Cancer and Blood Disease Institute (CBDI), the Vision Center and Inpatient Rehabilitation Services (Press release, Children’s Hospital Los Angeles, FEB 2, 2020, View Source [SID1234553750]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"This endowment expands the Petersen’s legacy of generosity by providing CHLA with a resource that will forever advance our mission to create hope and build healthier futures for children," says President and CEO Paul S. Viviano. "I am so grateful for this gift that will support a wide range of initiatives including research projects, technology upgrades, clinical care, key physician recruitment, capital projects, unreimbursed care and more."

The Margie and Robert E. Petersen Foundation, led by President GiGi Carleton, supports children’s health and well-being throughout Southern California, fulfilling the Petersen’s desire to care for the community by helping all children reach their full potential. Margie Petersen was a former CHLA Trustee, and both she and her husband Robert Petersen, founder and chairman of Petersen Publishing Co., were longtime supporters of the hospital. The Foundation has supported several CHLA programs and projects over the years, including an $8.5 million gift to open a state-of-the-art inpatient rehabilitation space in 2015, named the Margie and Robert E. Petersen Foundation Rehabilitation Center and honoring their sons Bobby and Richie Petersen.

"Through their transformative philanthropy and leadership, the Petersens dedicated their lives to helping children overcome obstacles of all kinds," says Alexandra Carter, CHLA Senior Vice President and Chief Development Officer. "They would be proud to know that this gift will help save children from debilitating illnesses by helping one of the nation’s top children’s hospitals provide families and patients the multidisciplinary, family-centered care they need."

In recognition of this transformative gift, CHLA will be naming the main driveway at its 4650 Sunset Boulevard campus the Margie and Robert E. Petersen Entry Plaza, in honor of Mr. Petersen’s role as founding publisher of Hot Rod and Motor Trend magazines and founder of the Petersen Automotive Museum.